GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound (GLAGOV)

Tracking Information
First Submitted Date ICMJE	March 15, 2013
First Posted Date ICMJE	March 19, 2013
Results First Submitted Date	December 4, 2017
Results First Posted Date	January 4, 2018
Last Update Posted Date	February 5, 2018
Actual Study Start Date ICMJE	April 18, 2013
Actual Primary Completion Date	July 12, 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 4, 2017)	Change From Baseline in Percent Atheroma Volume at Week 78 [ Time Frame: Baseline and week 78 ]; Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. The extent of atherosclerosis was expressed as percent atheroma volume (PAV) in a ≥ 40 mm segment of one targeted (imaged) coronary artery, calculated as the percentage of the total vessel volume occupied by atheroma.
Original Primary Outcome Measures ICMJE; (submitted: March 15, 2013)	Nominal change in PAV from baseline to 78 weeks post randomization, as determined by intravascular ultrasound (IVUS) [ Time Frame: 78 weeks ]
Change History	Complete list of historical versions of study NCT01813422 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 4, 2017)	Change From Baseline in Total Atheroma Volume at Week 78 [ Time Frame: Baseline and week 78 ]Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. Total atheroma volume (TAV) in a ≥ 40 mm segment of the targeted coronary artery was calculated as the average plaque area over the number of images that were evaluated by IVUS multiplied by the median vessel length to compensate for differences in segment length between participants.; Percentage of Participants With Regression in Percent Atheroma Volume [ Time Frame: Baseline and week 78 ]Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. The extent of atherosclerosis was expressed as percent atheroma volume (PAV) in a ≥ 40 mm segment of one targeted (imaged) coronary artery, calculated as the percentage of the total vessel volume occupied by atheroma. Regression in PAV was defined as any reduction from baseline in PAV.; Percentage of Participants With Regression in Total Atheroma Volume [ Time Frame: Baseline and week 78 ]Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. Total atheroma volume (TAV) in a ≥ 40 mm segment of the targeted coronary artery was calculated as the average plaque area over the number of images that were evaluated by IVUS multiplied by the median vessel length to compensate for differences in segment length between participants. Regression in TAV was defined as any reduction from baseline in TAV.
Original Secondary Outcome Measures ICMJE; (submitted: March 15, 2013)	Percentage of subjects demonstrating regression (any reduction from baseline) in PAV [ Time Frame: 78 weeks ]; Nominal change in normalized total atheroma volume (TAV) from baseline to 78 weeks [ Time Frame: 78 weeks ]; Percentage of subjects demonstrating regression (any reduction from baseline) in TAV [ Time Frame: 78 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound
Official Title ICMJE	A Double-blind, Randomized, Multi-center, Placebo-controlled, Parallel-group Study to Determine the Effects of Evolocumab (AMG 145) Treatment on Atherosclerotic Disease Burden as Measured by Intravascular Ultrasound in Subjects Undergoing Coronary Catheterization
Brief Summary	This study will evaluate whether low-density lipoprotein (LDL-C) lowering with evolocumab (AMG 145) results in greater change from baseline in percent atheroma volume (PAV) at week 78 than placebo in adults with coronary artery disease taking lipid lowering therapy.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Hypercholesterolemia
Intervention ICMJE	Biological: Evolocumab Administered by subcutaneous injection Other Names: AMG 145 Repatha®; Drug: Placebo Administered by subcutaneous injection
Study Arms	Placebo Comparator: Placebo Participants received placebo to evolocumab administered by subcutaneous injection once a month for 76 weeks. Intervention: Drug: Placebo; Experimental: Evolocumab Participants received 420 mg evolocumab administered by subcutaneous injection once a month for 76 weeks. Intervention: Biological: Evolocumab
Publications *	Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJ, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Scott R, Ungi I, Podolec J, Ophuis AO, Cornel JH, Borgman M, Brennan DM, Nissen SE. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. 2016 Dec 13;316(22):2373-2384. doi: 10.1001/jama.2016.16951.; Puri R, Nissen SE, Somaratne R, Cho L, Kastelein JJ, Ballantyne CM, Koenig W, Anderson TJ, Yang J, Kassahun H, Wasserman SM, Scott R, Borgman M, Nicholls SJ. Impact of PCSK9 inhibition on coronary atheroma progression: Rationale and design of Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV). Am Heart J. 2016 Jun;176:83-92. doi: 10.1016/j.ahj.2016.01.019. Epub 2016 Feb 17.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: January 21, 2015)	970
Original Estimated Enrollment ICMJE; (submitted: March 15, 2013)	950
Actual Study Completion Date	July 29, 2016
Actual Primary Completion Date	July 12, 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Clinical indication for coronary angiography; Subjects already taking statin therapy, niacin or ezetimibe at screening must have been on a stable dose for at least 4 weeks prior to screening LDL-C. Subjects not taking lipid-regulating therapy must enter the study via a lipid stabilization period. Subjects who are intolerant to statins must meet statin intolerance entry criteria; Fasting LDL-C ≥ 80 mg/dL (2.07 mmol/L) with or without additional risk factors, or, LDL-C ≥ 60 -< 80 mg/dL (1.55-2.07 mmol/L) in the presence of one major or three minor risk factors Subjects must meet the following criteria at the qualifying coronary catheterization procedure: Evidence of coronary heart disease (at least one lesion in a native coronary artery that has > 20% reduction in lumen diameter) or prior percutaneous intervention (PCI); Left main coronary artery < 50% reduction in lumen diameter by visual estimation; Target coronary artery for IVUS must be accessible to the IVUS catheter, must not have a > 50% reduction in lumen diameter within the target segment (and at least 40 mm in length); cannot have undergone prior PCI or coronary artery bypass graft (CABG) and is not a candidate for intervention over the next 18 months. It may not be a bypass graft, bypassed vessel or culprit vessel for previous myocardial infarction (MI). Exclusion Criteria: Coronary artery bypass graft surgery < 6 weeks prior to the qualifying IVUS; New York Heart Association (NYHA) III or IV heart failure, or last known left ventricular ejection fraction less than 30%; Uncontrolled cardiac arrhythmia that is not controlled by medications in the 3 months prior to randomization; Known hemorrhagic stroke; Uncontrolled hypertension at randomization; Fasting Triglycerides ≥ 400 mg/dL (4.5 mmol/L) at screening; Type 1 diabetes or poorly controlled type 2 diabetes (hemoglobin A1c [HbA1c] > 9%) at screening.; Moderate to severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 ml/min/1.73m²) at screening.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 99 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Australia, Belgium, Brazil, Canada, Chile, Czechia, Denmark, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Netherlands, Norway, Philippines, Poland, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Removed Location Countries	Czech Republic
Administrative Information
NCT Number ICMJE	NCT01813422
Other Study ID Numbers ICMJE	20120153; 2012-004208-37 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Amgen
Study Sponsor ICMJE	Amgen
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: MD Amgen
PRS Account	Amgen
Verification Date	January 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP